A

α-adrenergic receptors, 59

Abdominal A and B, 100

Abel, John Jacob, 51

acetylcholine, 208

receptors, 208, 209

ACTH (adrenocorticotropic hormone), 57, 65

actin fibers, 174, 189, 198

activation

of genes, 23, 24, 26, 80-90, 100, 101, 115, 115

of proteins, 23, 55, 67, 71, 74

acyl homoserine lactones (acyl HSL), 24-25, 29, 34

adaptation, 17, 20, 43, 48, 186-187, 189, 219-220

adaptor proteins, 68, 72, 73, 75, 77, 78-79, 153, 163, 175, 204, 209

Addison, Thomas, 49

Addison’s disease, 49, 51, 170

adenylyl cyclase, 61, 62, 63, 64, 66, 67, 132, 216

adhesion molecules, 196, 198-199, 202-203, 204, 205, 206, 225, 232, 238

adipocytes, 179-180, 184

adiponectin, 179, 182

adrenal glands, 49, 50, 67

adrenaline, 51, 52, 54, 56, 57, 58, 61, 67, 74, 77-78, 133, 141, 148, 170

adrenergic receptors, 55, 58-60, 61, 64, 65, 67, 74, 75, 77-78

Aer receptor, 14

Agouron Institute, 28

agouti-related peptide (AGRP), 180-181, 182

agrin, 208

Ahlquist, Raymond, 59

AI-2 receptor, 30

AI-2 signaling molecule, 29-30, 34

Akt, 173, 175

Albert Einstein College of Medicine, 63

Alexander, Christopher, 35-36, 75-76, 79, 247, 257-260

Alliance for Cellular Signaling

cell lines, 255-257

drug discovery goal, 247-250

funding, 243, 251, 257

Molecule Pages, 242

organization and design of experiments, 243-244

progress report, 252-254, 257

strategy and goals, 251-252

amino acids (see also individual amino acids)

hydrophobic, 13

neurotransmitters, 198

oligopeptides, 26, 29, 37

radiolabeled, 57

AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid), 198

receptors, 212, 216

amphibians, 83, 86-87, 105-109, 110, 111, 127, 136, 137

amygdala, 218, 219

anchoring proteins, 96

animal pole, 105

animalcules, 5

antagonist proteins, 110

Antennapedia, 100

anterior-posterior gradient, 94, 98-100, 107, 111, 113, 124-125, 126

antiapoptotic

drugs, 250

proteins, 132, 150, 163

antibodies, 227, 228, 238

antigens, 227, 229, 232, 234, 237

antitoxin receptors, 53, 58

Apaf-1, 130

APC (adenomatous polyposis coli) protein, 154-155

apical ectodermal ridge, 81, 124, 125, 126-127, 132, 134

apogenes, 160, 161

apoptosis

BMP and, 131

in cancer cells, 250

death ligands, 162-164

embryonic development and, 127-134, 163

homeostasis and, 149-150, 157-158, 165

lymphocytes, 227, 228

mutations and, 155, 158-160

apoptotic protease activating factor, 130

appetite, 177, 180-181, 182

arcuate nucleus, 182

Aristotle, 85

arsphenamine, 58

arteriometer, 50

aspartate, 14, 16, 37

AstraZeneca, 249

ATP (adeosine triphosphate), 16, 56, 61

attractants, 11, 14, 15, 17, 31

autoimmune disorders, 234-239

autoinducers, 22-23, 25, 29-30, 34, 37

autonomic nervous system, 53

autopod, 131

axons, 116, 117, 133-134, 189

B

β-adrenergic receptors, 59, 63, 65, 67, 74-75, 77-78, 132

β-arrestin, 67, 74-75

β-catenin, 108, 109, 111, 123, 136, 154-155

β-endorphins, 177

B lymphocytes, 145, 146, 227, 228, 232, 253, 255

Bacillus subtilis, 24-26, 67

bacteria (see also individual species)

antitoxin receptors, 53, 58

biofilm, 32-35, 45

chemotaxis, 9-10, 11, 12, 13, 14, 15-18, 23, 37, 74

cooperative communities, 21-27, 30-35, 42-43

culture environment, 19-21

detoxification pathway, 30-31

domains, 114

as eukaryote symbiotes, 45-46, 130

genetic diversity, 38

genetically engineered, 34

glucose/lactose metabolism, 90-91

Gram-negative, 25, 29

Gram-positive, 25-26, 29, 37

growth-inhibiting secretions, 33

language patterns, 27-30, 34, 38-39, 62, 67, 188

luminescent, 21-25, 28

marine, 19-25, 28-29

microcolonies, 30-35, 38-39

pathogenic, 29, 30-31, 53, 225-226

pilus, 32

quorum sensing, 21-27, 29, 34

and respiration, 41-42

spores, 26, 33

structure, 44

transcription factors, 25, 26, 90-91

virulence genes, 25

Bad, 131

Banting, Frederick, 170

Barzun, Jacques, 18

basal cell carcinoma, 151-152

basal cell nevus syndrome, 151

basal lamina, 208, 209

Bassler, Bonnie, 21, 23, 24, 25, 26, 28-31, 33, 34, 38

Bax, 131, 160

Bcl-2, 131, 151

Bcl-x_L, 131

Beachy, Philip, 114-115, 151-152, 249

Bell, Alexander Graham, 199

Berlin Institute of Pathology, 170

Best, Charles, 170

biased random walk, 10-12

bicoid gene, 96-97

Bicoid protein, 97, 98, 99

biodiversity, 52

biofilm, 32-35, 45

birds, 81-82, 110, 111, 122, 126

blastocoel, 105

blastoderm, 110

blastopore, 105, 106, 107, 109, 110

Bliss, Timothy, 215

blood cells (see also specific cells), 145-149

blood islands, 145

body weight, 176, 177, 179-184

bone marrow, 145, 147, 227, 235

bone morphogenetic proteins (BMP), 144

antagonists, 102 110, 111, 113, 131, 136, 137

and apoptosis, 131

BMP2, 110, 131

BMP4, 83, 110, 118, 131, 137

BMP7, 118, 131

and mesoderm induction, 107, 109, 136

as neuron chemoattractants, 204

structure, 101

Bonner, John Tyler, 3, 45, 93

Boron, 30

Borrelia burgdorferi, 29

Boston University, 254

Bourne, Henry, 253-254, 256

Bouvier, Michel, 251

brain, 117, 133, 193, 194, 209, 215, 238

Brand, Stewart, 185-186, 220, 239

breast cancer, 153, 164, 248, 250

Brown, Michael, 63

bubonic plague, 29

C

C. elegans, 163

c-fps gene, 70

c-kit, 248

cadherins, 198-199, 208

Cajal, Santiago Ramón y, 190-194, 195, 199-200, 201

calcium-binding proteins, 213

calcium–calmodulin-dependent protein kinases (CAM kinases), 213, 216

calcium channels (see also ion channels), 214-215, 216

calmodulin, 213

Cambridge University, 53

cancer (see also specific sites)

chemotherapy innovations, 247-250

chemotherapy resistance, 164

domains, 70-71

death ligands, 162-163, 164

Gorlin’s syndrome and, 151-152, 153-154

platform, 158, 159

polyps and, 154-155

metastasis, 164

mutations in signaling pathways and, 150-165

Cannon, Walter, 140, 141, 150, 167

CAP protein, 91, 175

carbon, 56

CART, 180-181, 182

Case Western Reserve University, 63

caspases, 129-130, 131, 160, 163-164

castration, 49

catalytic domains, 70, 72

catecholamines, 55

catenins, 199

caudal gene, 97

Caudal protein, 97, 99

caveolae, 175

Cbl, 175

ced-3 protease, 163

cell death (see apoptosis)

cell differentiation

amphibians, 107, 108

epigenesis, 85

eye development, 86-87

determination front, 122-123

embryonic development, 81-82, 83, 85, 86-87, 88-89, 92, 94, 104, 111, 112, 118-127, 142, 156

fruit flies, 98-102

lateral inhibition, 121

sexual, 2, 3

signaling pathways and, 88

stem cells, 143, 146

cell division, 123

cell membrane (see plasma membrane)

cell proliferation and maturation, 71, 89-92, 94, 101, 112, 123, 135, 136, 147

cell structure, 5, 44

(see also individual structures)

cell theory, 192

cell-to-cell communication (see also signaling pathways)

conservation principle, 76-77, 78

contingency-based changes in, 77-78

disruptions and disease, 6, 48-50, 150-165, 168

(see also cancer)

neurons, 51, 88, 117, 119-121, 188-189

pattern language, 35-39, 75, 76, 187, 190

principles of, 18

radioligand binding studies, 56-60, 61, 62

cellulose, 43

Cerberus, 83

cerebellum, 193

chaperone proteins, 13, 97-98

Charcot, Jean Martin, 237

Charron, Frédéric, 204

CheA enzyme, 15, 16, 17

CheB enzyme, 16-17

chemokines, 224, 225, 230, 234, 237, 238

chemotaxis

in bacteria, 9-10, 11, 12, 13, 14, 15-18, 23, 37-38, 74, 244

defined, 12

in green algae, 2, 3

signaling mechanisms, 13-18

chemotherapy, 58, 164, 247-250

CheR, 16-17

CheW, 15, 16

CheY, 15, 16, 23

chimeras, 114

chlorophyll, 41

cholcystokinin (CCK), 177-178

cholesterol, 52, 114, 151

Chordin, 83, 110, 113, 136, 137

chronic myelogenous leukemia, 248, 250

Ci (Cubitus interruptus), 115

coelem, 104

Cohen, Stanley, 133

colorectal cancer, 154-155, 164

Com X, 26

communication (see cell-to-cell communication; receptors; signaling pathways; specific proteins and cells)

confocal scanning microscope, 33

consensus sequences, 69, 90

contractile cells, 102

cooperation between organisms, 21-27, 30-35, 42-43

Cori, Carl and Getty, 55

corn lily (Veratrum californicum), 150-151

cortisol, 51, 52

Coulton, J. J., 84, 88, 92-93

CREB, 215, 216

cretinism, 50

CSF, 26

curare, 53, 54

Currie, Alistair, 129

cybernetics, 60

cyclic AMP (cyclic-3′,5′-adenosine monophosphate), 56, 57, 61, 62, 63-64, 66, 67, 213, 216

cyclic AMP protein kinase (see protein kinase A)

cyclopamine, 151

cyclopia, 150-151

cysteine-containing, aspartate-targeted proteases (see caspases)

cytochrome c, 130-131, 132, 160

cytokine receptors, 147-148

cytokines, 163, 178, 224, 227, 228, 232, 234, 237, 256

cytoplasm, 3, 15, 32

tyrosine kinases, 70-71

cytoskeleton, 43, 44, 51-52, 65, 174, 198, 199, 205

D

de Bordeau, Theophile, 49

de Meyts, Pierre, 172

death ligands, 162-164

Decapentaplegic, 101, 102, 137

deer, overpopulation, 155-156

Degradation Complex, 123, 154

Delta signaling molecule, 119-122, 133, 137, 206

dendrites, 189, 192, 194-195, 196, 198, 207, 209, 212, 216, 217, 220, 228-234

dermis, 143, 144

Desert hedgehog protein, 114

determination front, 122-123

development, 51

(see also embryonic development)

diabetes, type 1, 169, 170-171, 236

diabetes, type 2

complications, 168, 176

insulin signaling and, 168-169, 171-174

and obesity, 176, 179-180, 183-184

prevalence, 168

symptoms, 166-167, 171

treatment, 170-171, 175-177, 183-184

diphtheria, 53-54

Dishevelled protein, 123

Dispatched protein, 114-115

diseases (see also cancer; diabetes; mutations)

anti-infective agents, 58

cellular miscommunication and, 6, 48-50, 150-165

Dixit, Vishva, 161-162, 163, 164

DNA

binding, 90

damage, 131, 153

(see also mutations)

repair, 26, 153

structure, 90

domains

bacterial, 114

cancer-causing, 70-71, 248

catalytic, 70, 72

death, 163

defined, 68-69

in embryonic development, 93-94, 111, 112

intein, 114

interaction, 69-75, 78-79, 90, 153, 163, 187

dopamine, 52, 221

dorsal blastopore lip, 106-108

dorsal gene, 98

dorsal horn, 117

Dorsal protein, 97-98, 100-101

dorsal-ventral gradient, 94, 100-102, 107, 108, 111, 118, 125, 230

drugs

addiction, 177, 220-222

adrenergic-receptor-binding, 58-59

chemotherapy innovations, 247-250

G protein–coupled receptor blockers, 250-251

receptor affinity, 58-59

radiolabeled, 57, 58

tissue selectivity of, 53

Dustin, Michael, 232, 233

E

ectopic limbs, 81-82, 124

ectoderm, 86-87, 102, 104, 105, 106, 109-110, 111, 113, 116, 117, 121, 125, 136

effectors, 60-61, 62, 64, 66, 132, 163

Ehrlich, Paul, 52-54, 58, 247

electron microscope, 5

embryonic development (see also individual structures)

amphibians, 83, 86-87, 105-109, 110, 111, 136, 137

anterior-posterior gradient, 94, 98-100, 107, 111, 113, 124-125, 126

apoptosis, 127-134, 163

birds, 81-82, 110, 111, 122, 126

cell differentiation and maturation, 81-82, 83, 85, 86-87, 88-89, 92, 94, 104, 111, 112, 118-127, 142, 156

domains in, 93-94, 111, 112

dorsal-ventral gradient, 94, 100-102, 107, 108, 111, 118, 125

epidermis, 107, 110, 116-117, 118, 123

epigenesis, 46-47, 84-86

equivalence groups, 121, 128, 142

fibroblast growth factors and, 81-82, 83, 111, 113, 122-124, 125, 131-132, 134

fruit flies, 95, 96-102, 108, 113, 115, 119-120, 122, 123, 136-137

gastrulation, 102, 104, 105-109, 111, 122

germ layers, 104, 110, 111, 112

induction of mesoderm, 87-88, 107, 109, 111, 136

limb development, 81-82, 113, 122-127, 131-132, 134, 137

mammals, 83, 110, 111, 128

maternal effect, 99, 100, 101

modularity (patterning mechanism), 84, 94, 95, 112, 124-125-127

mutations, 93, 95-96

neurogenesis, 44, 102, 105-106, 107, 113-114, 116-122, 132-133, 137, 199-200, 202-204

nuclear divisions, 97

organizer, 107, 108, 109, 111, 116, 117

organogenesis, 110, 111, 112-127, 136

partitioning, 92, 94, 96, 98-99, 100, 101-102, 104-105, 107, 110, 112, 113

placenta, 110

polarity (spatial relationships between specialized tissues) and, 84, 88, 93, 94-100, 111, 112, 113, 122, 135

preformation, 85-86, 88-89

proximal-distal axis, 125-127

RNA transcription, 89-92, 96-100, 101, 109, 112, 115, 118, 119, 123, 135, 136

signaling molecules and pathways, 83, 92, 94, 99-102, 104-105, 107, 108, 110, 111, 112-127, 131-134, 135, 136, 152

stem cells, 145

Turing’s reaction-diffusion model, 87-88, 94-95

ventral-dorsal gradient, 118, 204

vertebrates, 112-114, 115, 116, 122, 124

zone of proliferating activity, 125, 126

endocrine system, 49, 51, 169-170, 177

endoderm, 102, 104, 105

endothelial cells, 142, 144, 147, 224, 225, 238

enzymes, 13, 15

(see also individual enzymes)

bioluminescent, 22, 25

separation from receptors, 55-56

Eph receptors, 206

ephrins, 202-203, 206

epidermal-dermal border, 143

epidermal growth factor, 144, 249

receptor, 153, 248

epidermis (see also skin)

basal layer, 143, 144, 152

embryonic development, 107, 110, 116-117, 118, 123

homeostasis, 143, 144-145

epigenesis, 46-47, 84-86

epinephrine, 58, 59

epithelial cells, 93-94, 135, 154, 191

epithelial sheets, 45-46, 102

equivalence groups, 121, 128, 142

erythrocytes, 145, 146

erythropoietin, 148-149, 178

Escherichia coli, 48

adaptation, 20, 187

chemotactic sensory apparatus, 9-10, 11, 12, 14, 15-16, 23, 37-38, 244

glucose/lactose metabolism, 90-91, 187-188

memory, 214

Esperanto, 27, 28, 34

estrogen, 51, 52, 148

eukaryotes

bacterial symbiotes, 45-46, 130

cell structure, 44

chemical communication, 43, 45, 49, 52, 62, 66-67, 68, 114

epithelial sheet, 45-46

evolution, 42-43, 45, 52, 68

gene expression, 89-92, 135

pattern language, 47-48, 76

selection for size, 46

signaling pathways, 70-77, 114

transcription factors, 89, 91-92

Euprymna scolopes, 21-25

Evan, Gerard, 152, 156, 157, 161, 164-165, 246, 248, 249

evolution, 42-43, 45, 52, 68

extracellular signaling, 71

eye development, 83, 86-87, 104, 205-206

F

Fas, 163

FasL, 164

FADD (Fas activated death domain), 163-164, 234

Fairmount Park (Philadelphia), 155

fat cells, 177, 178, 179, 180-181, 182

fatty acids, 173, 178, 179

feeding behavior, 177-178, 180-181, 182

fibroblast growth factors (FGF)

and embryonic development, 81-82, 83, 111, 113, 122-124, 125, 131-132, 134

FGF2, 144

FGF4, 125, 134

FGF7, 144

FGF8, 124, 125, 134

FGF10, 124, 125

receptors, 153

and wound healing, 144

fibroblasts, 143, 144, 224

fight-or-flight response, 139-141

filopodia, 212

Finger, Stanley, 191-192

Fischer, Edmond, 55

flagella, 2, 3, 9-10, 11, 12, 13, 14, 16, 31, 32, 188

Flanagan, John, 113

flatworms, 102

flotillin, 175

follistatin, 110

Food and Drug Administration, 239

fps gene, 70, 153

Fps kinase, 70

Friedman, Jeffrey, 177-179, 183, 184

Frizzled receptor, 123

fruit fly (Drosophila melanogaster)

cell differentiation, 98-102

development, 95, 96-102, 108, 113, 115, 119-120, 122, 123, 136-137, 230

G

G protein–coupled receptors, 65-67, 77, 148, 205, 224, 250-251

G protein–coupled receptor kinase (GRK), 67, 74, 78

G proteins, 62-65, 67, 77, 78

GABA (gamma-aminobutyric acid), 209

galactose, 14

Galen, 169

ganglion, 134

Gann, Alexander, 69-70, 136

gap genes, 99, 100

gastric bypass surgery, 180

gastrointestinal stromal tumor, 248

gastrulation, 102, 104, 105-109, 111, 122

gene expression (see also transcription factors)

activators, 23, 24, 26, 80-90, 115

in biofilm, 33

for cell proliferation and maturation, 71, 89-92, 94, 101, 112, 123, 135, 136, 147

environment and, 20-21, 33

eukaryotes, 89-92, 135

repressors, 89-90, 91, 115, 122

gene products, 69-70, 79, 96

(see also proteins; individual gene products)

gene regulatory proteins, 100, 108

Genentech, 162, 248

genes (see also mutations; specific genes)

activation, 100, 101, 115

(see also gene expression)

cloning, 178

competence, 26

gap, 99, 100

homeotic selector, 100

maternal effect genes, 99, 100, 101

naming, 98

pair-rule, 99, 100

proliferation, 163

receptor cloning, 59

genetic engineering, 83

genome, as design blueprint, 88-89, 91

Gerhart, John, 76, 79

germ cells, 2

germ layers, 104, 110, 111, 112

giant marine snail (Aplysia californica), 213-214, 216, 219

Gilbert, Scott, 96, 136

Gilman, Alfred Goodman, 54, 55, 56, 62-65, 78, 241-244, 247, 251-252, 255, 256, 257

Gleevec, 248-249, 250

Gli-1, -2, and -3, 115

glial cells, 116, 205

glioblastoma, 115

glucagon, 61

glucose

bacterial metabolism, 90-91, 187-188

homeostasis, 67, 165-169, 171, 173, 174, 176, 179, 180, 184

insulin and, 168, 179, 184

transport protein, 174-175

GLUT4, 174-175

glutamate, 198, 209, 212, 213, 216

glycogen, 54, 175

glycogen phosphorylase, 54-55, 56, 67

glycoproteins, 32, 34

God, 85

Golgi apparatus, 44

Golgi stain, 193, 200

Golgi, Camillo, 193

gonidia, 2, 3

Gonium, 1-2

Goodman, Louis S., 63

Gorlin’s syndrome, 151-152, 153-154

granulocytes, 146, 147

Graves’ disease, 236

Grb2 adaptor protein, 73

Green, Douglas, 152

green algae, 2, 3

Greenberg, E. Peter, 45-46

growth factors, 52, 75

(see also specific growth factors)

as cell survival factors, 132-133

receptors, 71, 72, 73, 78, 153

GTPases, 62, 72, 153, 204

guanine nucleotide binding, 62, 64

guanosine diphosphate (GDP), 62, 64, 66, 72

guanosine triphosphate (GTP), 61-62, 64, 66, 77

gut lining, 142, 154

H

Haemophilus influenzae, 29

halteres, 100

Hamburger, Viktor, 133

Hanafusa, Saburo, 71

Harrison, Ross, 199, 200

Harvard University, 22, 31, 135, 211

Harvey, William, 84-85

Hastings, John Woodland, 22

Hawaiian bobtail squid, 21-25

Hayden Planetarium, 63

Hedgehog proteins, 83, 99-100, 113-114-115, 123, 137, 150, 153

Heliobacter pylori, 29

hemoglobin, 148-149

Hensen, Viktor, 200

Henson’s node, 111

HER2 protein, 250

her2/neu gene, 248

Herceptin, 248, 249, 250

Herophilus of Chalcedon, 169

hippocampus, 215, 218

histamine, 224

histidine, 16, 26

homeostasis

apoptosis and, 149-150, 157-158, 165

blood, 142, 145-149

and body weight, 176, 177, 180-184

defined, 140

epidermis, 142, 143, 144-145

FGFs and, 144

fight-or-flight response, 139-141

glucose, 67, 165-169, 171, 173, 174, 176, 179, 180, 184

injury repair, 144-145, 157

(see also immune system)

mutations and, 152, 154, 156-157

signaling pathways, 141, 142, 144, 146

skin, 142, 143-145

stomach lining, 142

stem cells and, 142, 143, 144, 145-150

honeybees, 21

hormones, 49, 51, 52, 67, 188

(see also individual hormones)

radiolabeled, 57

receptors, 54, 55, 65, 75, 148, 171-172

Hox (homeotic selector) genes, 100, 124

Hughson, Fred, 30

human genome, 4, 88-89, 91

Human Genome Project, 178

humors, 48-49

hunchback, 97

Hunchback, 97, 99

Hydra, 102-103, 136

hydrogen, 56

hydrogen sulfide, 41

Hyman, Steven, 211, 222

hyperthyroidism, 236

hypothalamus, 180-181, 182

hypothyroidism, 170

I

idiosyncratic drug reaction, 63

immunoglobulins, 226, 227

immune system, 52, 223-224

(see also individual cells and components)

adaptive, 226-228, 229, 234, 235

autoimmune disorders, 234-239

dendrites and, 228-231

inflammation, 225, 234-239

innate, 225, 234, 235

response to injury or infection, 224-228

synapses, 231-234

Indian hedgehog protein, 114

inflammation, 225, 234-239

information theory, 60

insulin, 51

and body weight, 176, 179-180, 182

discovery, 170

glucose metabolism, 168, 179, 184

receptors, 171-172, 173-174, 175, 244

resistance, 175, 179-180, 184

(see also diabetes, type 2)

role of, 168, 173

sensitivity, 179

signaling pathway, 148, 168-169, 171-175, 176, 244

integrin receptors, 202-203, 205, 225, 238

intein, 114

interaction domains, 69-75, 78-79, 90, 153, 163, 187

interferon-gamma, 237

interleukin-1β-converting enzyme (ICE), 163

interleukin-2, 237

interleukin-3, 148, 178

interleukin-9, 148, 178

interneurons, 116, 117, 118, 194, 202

iodine, 56

ion channels, 88, 189, 207

ion pumps, 88

Iressa, 249, 250

IRS (insulin receptor substrate), 172, 175

islets of Langerhans, 170, 171

isoproterenol, 59, 63, 64

J

Jacob, François, 90-91

Janus kinases (JAKs), 148

Johns Hopkins University School of Medicine, 154, 170

Joslin Diabetes Center, 146, 172

K

Kahn, Ronald, 172, 173, 175, 244

Kandel, Eric, 213-214, 215, 216, 217, 219

keratin protein, 143

keratinocytes, 143, 144, 224

Kerr, John, 129

kinases, 15, 16, 18, 26, 55, 67-68, 77, 79, 101, 213

Kinzler, Ken, 154

Kirschner, Marc, 76, 77, 78, 93, 98-99, 112, 113, 135

knockout mice, 83

Kolter, Roberto, 31, 32-33, 34, 38

Krebs, Edwin, 55

Krieg, Mary Jane, 177

L

labial, 100

lac repressor, 91

lactose, 90-91

Lai, Eric, 118

laminins, 202-203, 205, 209

Langerhans, Paul, 170

Langley, John Newport, 53-54

lateral inhibition, 121

Lazar, Mitchell, 179, 183-184

Lazebnik, Yuri, 130

Le Doux, Joseph, 219

learning (see memory and learning)

Leeuwenhoek, Anton van, 5

Lefkowitz, Robert, 57-58, 60, 63, 66

leptin, 178, 179, 180-182

receptors, 183

resistance, 184

leukemia, 153

Levi-Montalcini, Rita, 133

life ligand, 163

ligand binding, 13-14, 17

limb buds, 81-82, 113, 124, 126

linker proteins, 68

lipid rafts, 175

lipids, 114

liver cells (hepatocytes), 62, 67, 74, 142

Llinas, Rodolfo, 10

logorrhea, 152

Lømo, Terje, 215

Love, Susan, 248

luciferase, 22

luminescent bacteria, 21-25, 28

lung cancer, 153, 164, 249

lupus, 236

luxI, 23

LuxI, 25, 28-29

luxR, 23

LuxR, 23, 25, 28-29

LuxS, 30

Lyme disease, 29, 155

Lymphocytes (see B lymphocytes; T lymphocytes)

lymphoma, 153, 164

M

MacArthur Foundation, 23

macrophages, 147, 224, 228, 234, 256

Maddox, John, 246

magnesium channel, 216

(see also ion channels)

major histocompatibility complex, 229, 231, 232

mammals (see also homeostasis)

embryonic development, 83, 110, 111, 128

grazing animals, 12

reproduction, 127

Mangold, Hilde, 106

MAP kinases, 71-72, 73, 74-75, 132, 153, 215, 216

MAPK, 72

MAPKK, 71-72

MAPKKK, 71

marine bacteria, 19-25, 28-29

mass spectrometry, 30

mast cells, 224, 225, 234

maternal effect genes, 99, 100, 101

matrix proteins, 208

medullablastoma, 151

megakaryocytes phagocytes

memory and learning

and adaptation, 219-220, 221-223

biological basis, 210-220

and drug addiction, 220-222

emotional, 217-220

explicit, 215-216

fear conditioning, 217-220, 222

immunological, 229-231

long-term, 214

primitive bacterial, 17, 214

short-term, 214, 217

signaling pathways, 215-223

Aplysia, 213-215, 218

mesoderm, 103-106, 113, 117, 122, 123, 124, 145

induction, 87-88, 107, 109, 111, 136

metazoans, 43, 45, 67

(see also embryonic development)

tripartite organization, 102

methyl groups and methylation, 17, 23, 30, 74

Minkowski, Oskar, 170

mitochondria, 42, 44, 130, 131, 132, 150, 160, 164

mitogen-activated protein kinases (see MAP kinases)

monoclonal antibodies, 248

Monod, Jacques, 90-91

morphogens, 87-88, 94-95, 96-97, 99, 113, 125

motor neurons, 113, 117, 122, 196, 208-209

Mount Sinai Hospital (Toronto), 70

mouse

B lymphocyte, 241-242

hematopoietic stem cells, 146

knockout, 83

monocyte, 241-242

ob/ob, 178, 179, 180

movement

biased random walk, 10-12

chemical direction of (see chemotaxis)

flagella, 2, 3, 9-10

random walk, 10

mRNA, 96-97, 108, 217

multiple myeloma, 153

multiple sclerosis, 236-239

muscle cells, 88

mutations, 6

and adaptation, 187

and apoptosis, 155, 158-160

accumulation of, 154

and cancer, 150-165

cyclopia, 150-151

fruit fly studies, 93, 95-96

and homeostasis, 152, 154, 156-157

longevity of cells and, 154

naming genes for, 98, 99, 100

obesity, 178

in oncogenes, 158, 159

pathogens, 226

in receptor tyrosine kinases, 153

myc gene, 246

Myc transcription factor, 159, 160-161, 163, 164, 245-246

myelin basic protein, 236-237

myelin-oligodendrocyte glycoprotein, 236

myelin proteolipid protein, 236

Myf-5, 123

myoblasts, 123

myocytes, 253-254, 255

MyoD, 123

myofibroblasts, 144

myotome, 123

myotubes, 208, 209

N

N protein (see G protein)

N-(3-oxohexanoyl)-homoserine lactone, 22

nanos, 97

Nanos, 97, 99

natalizumab, 238-239

National Cancer Institute, 243

National Institute of Allergy and Infectious Diseases, 243

National Institute of General Medical Sciences, 243

National Institute of Mental Health, 211

National Institutes of Health, 63, 231

natural killer cells 145, 227, 228, 231-232

Nealson, Kenneth, 22

nerve growth factors, 133-134

nervous system (see also neurons; other individual components)

action potential, 189, 195, 197, 198, 208

adaptation, 209-210

adhesion molecules, 196, 198-199, 202-203, 204, 205, 206, 207

architecture of neurons, 193, 194-195

autonomic, 53

behavior coordination, 177-178, 180-181, 182, 211

development, 44, 102, 105-106, 107, 113-114, 116-122, 132-133, 137, 199-200, 202-204

ion channels and pumps, 88, 189, 196, 198, 207, 212-213, 216

myelin sheath, 194, 236-239

neuromuscular junction, 207-209

neurotransmitters and receptors, 57, 190, 197, 198, 199, 207, 208, 215

peripheral, 133, 199-200, 238

postsynaptic density, 198, 207

principle of dynamic polarization, 195

reticular theory, 193, 194

retinal development, 205-206

signaling pathways, 51, 52, 57, 117, 180-181, 189, 190, 191, 194-199, 207, 215-223

Aplysia, 213-214, 215, 216

synapses, 195-198, 202, 206-210

Nestler, Eric, 221

neural plate, 116-117

neural tube, 117-118, 122, 200

neuregulin, 208

neurexins, 198

neurolignin, 209

Neurological Society of Great Britain, 53

neuromuscular junction, 207-209

neuropeptide Y (NPY), 180-181, 182

neurons (see also nervous system)

axons, 116, 117, 133-134, 189, 192, 194-195, 196, 197, 199, 200-203, 204-210, 236

cell-to-cell communication, 51, 117, 188-189

chemoattractants, 202-204

commissural, 202-203, 204

connections, 216-217

dendrites, 189, 192, 194-195, 196, 198, 207, 209, 212, 216, 217, 220, 228-234

electron microscope studies, 196-196

excitatory, 216

Golgi stain, 193-194, 200

growth cones, 200-203, 204-205, 206

immune response, 228-231

interneurons, 116, 117, 118, 194, 202, 214, 215

long-term potentiation, 215-216, 219

memory recorded in, 210-223

migration and synapse formation, 200-210

motor, 113, 117, 122, 196, 202, 208-209, 215

mRNA transcripts, 217

secretory apparatus, 196-197, 198, 207, 214-215

sensory, 117, 119-121, 194-195, 214-215, 224, 225

spines, 212, 216

tissue culture, 199, 200, 209

neurotransmitters, 57, 190, 197, 198, 207, 208, 209, 221, 244

netrins, 202-204

neutrophils, 224

New York University, 232

newt, 106

NF-κB, 163, 164, 234

nickel, 14, 16

nicotine, 53, 54

Nieuwkoop center, 107

Nirenberg, Marshall, 63

nitric oxide, 51

Niu, M. C., 108

NMDA (N-methyl-D-aspartate), 198

receptors, 212-213, 216

Nobel laureates, 54, 55, 65, 199, 214

Nodal-related proteins, 107, 108, 109, 111

Noggin, 83, 110, 113, 131, 136

norepinephrine, 52, 59

Northeastern University, 19-20

notch gene, 122

Notch receptor, 119-122, 133, 137, 146

notochord, 117

Novartis, 248

nuclear magnetic resonance spectrometry, 14

nucleotides, 56, 61, 72

binding sites, 62

guanine (see G protein)

radioactive, 57

Nusse, Roel, 123

Nüsslein-Volhard, Christiane, 96

O

ob gene, 178

Ob protein, 178

obesity, 176, 178-180, 182, 183-184

olfactory bulb, 193

oligodendrocytes, 236, 238

oligopeptides, 26, 29, 37

Oliver, George, 50

oncogenes, 153, 155, 158, 160

Opie, Eugene, 170

optic tectum, 205, 206

optic vesicles, 83, 86-87, 105, 106

organelles, 44

organizer, 107, 108, 109, 111, 116, 117

organogenesis, 110, 111, 112-127, 136

Osterfield, Miriam, 113

ovarian cancer, 153

ovarian follicle, 98

ovaries, 49, 51

oxygen, 14

P

p53 protein, 159, 160, 162

pain, 225

pair-rule genes, 99, 100

palmitate, 114, 123

pancreas, 49, 51, 168, 169-170, 180, 184

Pander, Christian, 104

parasegments, 98-99, 100, 113, 123

Pastan, Ira, 57

Patched receptor, 115, 151-152, 153

pathogens, 29, 30-31, 53, 225-226, 230

Pawson, Tony, 70-73, 156

Pennsylvania Audubon Society, 155

peptide, 51, 52

bonds, 13

hormones, 52, 58, 177-178

receptors, 14

The Pharmacological Basis of Therapeutics, 63

peripheral nervous system, 133, 199-200

phagocytes, 145, 146, 224, 225, 227

phosphatidylinosotol-3-kinase, 132

phospholipase C, 62

phospholipids, 60

phosphorus, 56

phosphorylase kinase, 55, 67, 74

phosphorylation, 15, 16, 26, 67, 71, 73, 101, 148, 172, 214, 216

phosphotyrosines, 173, 175

photosynthesis, 41-42

PI3 kinase, 132, 173, 175

pilus, 32

PIP3, 132, 160, 175, 254

pituitary gland, 57

placenta, 110

plants, 21, 43, 136

plaque, dental, 34

plasma membrane, 13, 14, 18, 37, 43, 44, 47, 51-52, 54, 59-60, 65, 77, 97, 99, 129, 174, 175, 196

platelet derived growth factor (PDGF), 144, 153

receptor tyrosine kinase, 248

platelets, 144, 145, 146, 224

polypeptides, 64, 101

polyps, 154-155

POMC, 180-181, 182

preformation theory, 85-86, 88-89

primary brain vesicles, 117

primitive streak, 110

Princeton University, 29

proapoptotic proteins, 132, 160, 164

progesterone, 51, 52, 148

prokaryotes, 43, 48, 67

(see also bacteria)

promoter sequence, 89

proneural genes, 119-121

prostaglandins, 224

protein kinase A (PKA), 67, 74, 214, 215

proteins (see also individual proteins and classes of proteins)

activation, 23, 55, 67, 71, 74

architecture, 12-13, 18, 36-37, 39, 48

binding sites, 13-14, 69-70

(see also ligands; receptors)

catalytic, see enzymes

chemotaxis, 15-18, 37

chimeras, 114

connecting, 68, 69-70

dimers, 14

domains, 68-75

folding, 13, 30, 68-70, 114

master switches, 123

receptor-like, 114-115

relay, 101

splicing, 114

protists, 1

proximal-distal axis, 125-127

Pseudomonas aeruginosa, 25

Ptashne, Mark, 69-70, 136

Purkinje cells, 116, 194

pyramidal cells, 116, 194

Q

quorum sensing, 23-27, 29, 34

R

radioactive isotopes, 56-57

radiolabeled

amino acids, 57

drugs, 57, 58

radioligand binding studies, 56-60, 61, 62

Raff, Martin, 132

RAG proteins, 226, 227, 234

Raine, Cedric, 236, 239

Rall, Theodore, 55, 56, 63

Rana fusca, 86

random walk, 10

rapsyn, 208, 209

Ras, 72, 73, 153, 160

Raspail, Francois-Vincent, 5

RAW264.7 cell line, 256

receptor kinases, 101

receptors

activation of proteins, 23, 55

affinity for drugs, 58-59

α-adrenergic receptors, 59,

antigen, 227, 229, 233-234

antitoxin, 53, 58

architecture, 13-15

β-adrenergic receptors, 59, 63, 65, 67, 74-75, 77-78, 132

bone morphogenetic protein, Type I, 101

bone morphogenetic protein, Type II, 101

chemotaxis, 14-18, 74

cloning genes for, 59

clusters, 208

cyclic-AMP-dependent, 57-58

cytokine, 147-148

for death ligands, 163, 164

decoy, 164

G protein–coupled, 64, 65-67, 148

on growth cones, 204-205

growth factor, 71, 72, 73, 78, 153

hormone-activated (endocrine), 54, 55, 65, 75, 148, 171-172

(see also adrenergic receptors; insulin)

isolation of, 55-56, 59

light, 62, 66

odor, 62

pairbonding, 73, 172

pathogen-recognition, 224, 225, 230

pioneering work, 52-60

quorum sensing, 23-24, 25, 26

radioligand binding studies, 56-60, 171

second messengers, 55-56, 60-65, 67, 79

sensitivity, 17, 18, 23, 74, 98

structure, 65-66, 77-78

transmembrane, 37, 54, 59-60, 65-67, 77, 188, 227

tyrosine kinase, 73, 132, 133-134, 153, 163, 172, 208, 248

subtypes, 59

recombinase, 226

red blood cells, 88, 142, 147, 148

(see also erythrocytes)

repellants, 11, 14, 15

reproduction

green algae, 2, 3

mammals, 127

plants, 21

resistin, 179

respiration, 41-42

Reynolds, Barbara, 175-176

rheumatoid arthritis, 236

rhodopsin, 62, 66

rhomboid gene, 102

ribose, 14

RNa-binding proteins, 98

RNA interference, 255, 256

RNA polymerase, 89, 90

Rockefeller University, 177

Rodbell, Martin, 60-62, 63, 65

Roth, Robert, 57

Royal Society, 53, 195

S

S49 lymphoma cell line, 63-64

S-adenosylhomocysteine, 30, 37

S-adenosylmethionine, 30

Salmonella species, 29

Saltiel, Alan, 171, 174

Salvarsan, 58

Samuel Lunenfeld Research Institute, 70

Sanes, Joshua, 207, 208, 209-210

scaffolding proteins, 68, 72-73, 78-79, 90, 163, 208-209

(see also Adaptor proteins)

Schäfer, Edward Albert, 50, 51

Schleiden, Jacob, 192

Schneider, Bruce, 177

Schwann, Theodor, 192

Schwann cells, 238

secretin, 51

secretory cells, 196

selectins, 225

serine, 14, 37, 68, 101, 213

serine-threonine receptor kinases, 101

sexual differentiation, 2, 3

SH2 (Src-homology 2) interaction domain, 71, 72, 73, 78, 148, 173, 204

SH3 (Src-homology 3) interaction domain, 71, 72, 73, 78, 204

Sharpey, William, 50

Shaw, Andrey, 233

sheep, cyclopia in, 150-151

Sherrington, Charles, 192, 195

Siamese twins, 83, 106-107

signaling pathways (see also cell-to-cell communication; receptors)

activation, 115-116

as agents for change, 187

amplifier component, 60-61

(see also effectors)

for apoptosis, 131-134, 157, 161-165

autoinducers, 22-23, 25, 29-30, 34, 37

in body weight control, 180-184

cell differentiation and, 88

in chemotaxis, 13-18

costimulatory signals, 229

death ligands, 162-163, 164

detoxification, 30-31

in drug addiction, 220-222

in embryonic development, 83, 92, 94, 99-102, 104-105, 107, 108, 110, 111, 112-127, 131-134, 135, 136, 152

eukaryotes, 70-77, 114

extracellular, 71, 135

FGF10–FGF8 feedback loop, 124-125

flexibility in, 37-38, 78-79

GTPases and, 62

in homeostasis, 141, 142, 144, 146

in immune response, 229-231

insulin, 148, 168-169, 171-175, 176

interactive nature of, 245-247, 260

interaction domains, 69-75, 78-79, 90

intracellular, 119, 123

in limb development, 124-125, 127

master switches, 123

mathematical modeling, 246-247

in memory and learning, 210-223

molecular “words,” 4

mutations in, 150-165

in neurogenesis, 116-119

Notch-Delta, 119-122, 133, 137, 146

organizer, 107, 108

protein “sentences,” 4-5, 15-17, 67

research accomplishments, 244-245

reward, 221-222

second messengers, 55-56, 60-65, 67, 79, 115, 132, 160

sensor (discriminator) component, 37, 60

(see also receptors)

stem cell mobilization, 144-145, 146

subversion of, 152-155

time delaying, 115-116

transcription factors and, 89-92, 96-100, 115-116, 119, 148

transducers, 61-65, 77, 119, 148, 171-172

(see also G proteins)

two-component relay, 26, 29

virtual cell, 241-242

(see also Alliance for Cellular Signaling)

Silverman, Mike, 28-29

Simarro, Don Luis, 193

Simpson, Paul, 254

skin

cancer, 151-152

damage and repair, 142, 143-145

development, 105-106, 116

stem cells, 152

structure and components, 143

Smad protein, 101

Smith, Temple, 254

Smoothened protein, 115, 151, 152, 153

snail gene, 101

Snail protein, 102

sog gene, 102

Sog protein, 102, 137

somatic cells, 2, 3

somites, 122-123, 124

Sonic hedgehog protein, 83, 114, 117-118, 125, 126, 146, 151, 152, 204

SOS, 72

Spemann, Hans, 86-87, 104, 105, 106, 108

spinal cord, 117, 134, 194

src gene, 70, 153

Src protein, 70-71

St. Mary’s Hospital (Middletown, PA), 175

staining techniques, 53, 58

STAT (signal transducers and activators of transcription), 148

steady state output, 17

Steel (stem cell factor), 148

Steinman, Ralph, 228-229, 230, 234

stem cells

apoptosis, 149-150, 173

and cancer, 152, 154

development, 145

differentiation, 143, 146

(see also fibroblasts)

hematopoietic, 145-150, 154, 178

and homeostasis, 142, 143, 144, 145-150

lineage-restricted, 147

lymphoid progenitor, 147

myeloid progenitor, 147, 148

reservoir, 143

signaling pathways, 144-145, 146, 147-148

skin repair, 143-144, 152

Stock, Ann, 10, 12, 17-18, 20

Streptococcus species, 29

stromal cells, 147

Stull, Jim, 253

Sutherland, Earl, 55, 56, 57, 60, 63, 67

synapses

adding, 215

excitatory, 212

formation, 200-210

immunological, 231-234

pruning, 212

sensitization, 214-215, 216, 219

signaling, 189

synaptic cleft, 208

synaptic vesicles, 196, 197-198, 208-209

syncytium, 97

T

T lymphocytes, 145, 146, 227, 228, 229-239

Tabin, Cliff, 82, 124, 127, 134

Takamine, Jokichi, 51

Tar receptor, 14-15, 16

Tap receptor, 14

Tessier-Lavigne, Marc, 204

testes, 49, 51

testosterone, 51, 52

tetanus, 53

threonine, 68, 101

thymus, 227, 230

thyroid gland, 49, 50, 51

thyroxine, 51, 148

Time-Life Nature and Science Library, 161-162

tissue culture, 199-200, 209

Toll-like receptors, 230

TRADD, 163-164

transcription factors, 143, 151

in bacteria, 25, 26, 90-91

and embryogenesis, 89-92, 94, 96-100, 101, 109, 112, 115, 118, 119, 123, 135, 136

eukaryotes, 89, 91-92

fruit fly, 96-100, 101, 115

gene regulation, 23, 25, 26, 71, 115, 119, 148, 215

mutations in, 160-161

as receptors, 66

structure, 90

vertebrates, 115

transforming growth factor-β (TGF-β), 101, 109, 118, 144

transmembrane proteins, 115, 188

Trg receptor, 14

TrkA receptor, 133-134

Tsr receptor, 14

tumor necrosis factor, 162-163, 234, 237-238

receptor, 162, 164

tumor promoters, 164

tumor suppressor genes, 153

tumor virus, 70, 71

tumorigenesis, 154

Turing, Alan, 87-88, 94

Turing’s reaction-diffusion model, 87-88, 94-95

twist gene, 101-102

Twist protein, 102

Twitty, Victor, 108

tyrosine, 52, 68

tyrosine kinases, 70-75, 148, 153

Tysabri, 239

U

ulcers, 29

Ultrabithorax, 100

unicellular organisms, 1-3

universal language, 27-30, 34

University of California, San Francisco, 156, 253, 254

University College London, 50

University of Iowa College of Medicine, 46

University of Pennsylvania, 179, 201

University of Strasburg, 170

University of Würzburg, 86

University of Zaragoza, 190

U.S. Department of Agriculture, 151

V

V-CAM1, 238

v-fps gene, 70

vascular endothelial growth factor (VEGF), 144-145

vegetal pole, 105

ventral-dorsal gradient, 118, 204

ventral horn, 117

Veratrum californicum (corn lily), 150-151

vertebrates, 112-114, 115, 116, 122, 124

VFA-4, 238

Vibrio cholerae, 29, 31

Vibrio fischeri, 21-25, 28-29, 67

Vibrio harveyi, 28-29

virtual cells, 241-242, 254

viruses, 226, 230

Vogelstein, Bert, 154

Volvocacae, 1

Volvox cartieri, 1-2, 3, 102

von Mering, Joseph, 170

W

Wagers, Amy, 146, 154

Washington University at St. Louis, 162, 207

WEHI-231 cell line, 253, 255

Weinberg, Robert, 156

Weinmaster, Gerry, 119

Werner, Eric, 246

white blood cells, 129

(see also phagocytes)

White, Morris, 172

Wiener, Norbert, 60

Wieschaus, Eric, 96

Winans, Stephen, 26

Wingless protein, 123, 137

Wirsüng, Johann Georg, 169-170

Wnt 7A, 125

Wnt proteins, 123, 125, 131-132, 136, 137, 146, 150, 154, 155

Wolff, Caspar Friedrich, 86

Wolpert, Lewis, 95, 111, 125-127

Wylie, Andrew, 129

X

x-ray crystallography, 14, 30, 65

Xnr protein, 107, 109

Y

Yersinia pestis, 29

Z

Zamenhof, Ludwig L., 27, 28

zone of proliferating activity, 125, 126